In the name of God

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DEFINITION OF ANEMIA

• Anemia may be defined as a reduction in red blood
  cell mass or blood hemoglobin concentration.
• It is particularly important to use age and sex
  adjusted norms when evaluating a pediatric
  patient for anemia

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Normal limit of Hb in children
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CLASSIFICATIONS OF ANEMIA

• Physiologic classification
• Morphologic classification
• Mean corpuscular volume

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Anemia

• Blood loss (acute) Normal spleen, high retic
  count, normal bilirubin, normal urinalysis
• Hemolytic anemia Splenomegaly, increased
  reticulocyte count, high bilirubin (indirect),
  urobilinogen or hemoglobinuria
• Impaired red cell formation Normal spleen, low
  retic count, normal bilirubin, normal urinalysis

• Retic, bilirubin, spleen, U/A,

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Approch to anemia blood loss(Acute) (Normal
spleen, high retic count, normal bilirubin,
normal urinalysis)

• Neonatal problem (fetofetal transfusion,
  fetomaternal transfusion,)
• Hemorrhagic disease of newborn
• Meckels diverticulum, ..

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Anemia

• Blood loss (acute)
• Hemolytic anemia Splenomegaly, increased
  reticulocyte count, high bilirubin (indirect),
  urobilinogen or hemoglobinuria
• Impaired red cell formation

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Approch to anemia Hemolytic anemia
(Splenomegaly, increased reticulocyte count, high
bilirubin (indirect), urobilinogen or
hemoglobinuria)

• 1) Corupuscular
• 2) Extra corpuscular

• Enzyme defect,
• Membrane defect,
• Hemoglobin disorder

• immune,
• non immune

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Hemolytic anemia Corpuscular

• 1) Enzyme defect

• G6PD deficiency
• PK deficiency

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Glucose 6 phosphate dehydrogenase(G6PD)
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G6PD DEFICIENCY

• X-linked disorder
• Affecting 200 to 400 million people
• Contains 515 amino acids
• Over 400 variant enzymes have been reported (90
  according to specific mutations)

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Classification of G6PD variants

•  Class I variants are rare, have severe enzyme
  deficiency (less than 10 percent of normal) and
  have chronic hemolytic anemia(44 variants)
• Class II variants have severe enzyme
  deficiency, but there is usually only
  intermittent hemolysis (28 variants)
•  Class III variants have moderate enzyme
  deficiency (10 to 60 percent of normal) with
  intermittent hemolysis usually associated with
  infection or drugs (16 variants)
• Class IV variants have no enzyme deficiency or
  hemolysis(2 variants)
• Class V variants have increased enzyme activity
         

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PATHOPHYSIOLOGY OF G6PD DEFICIENCY

• The in vivo half-life of enzyme normal enzyme
  (G6PD B) 62 days, G6PD A- 13 days, G6PD
  Mediterranean in hours
• G6PD A- Patients usually have hemolysis that is
  mild and limited to older deficient erythrocytes
  (class III).
• G6PD B(Mediterranean) red cells of all ages are
  grossly deficient (class II).

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DIAGNOSIS

• Clinical presentation (should be considered in
  the differential diagnosis of any nonimmune
  hemolytic anemia)
• Laboratory findings Hemolysis (Hb, Retic count,
  bilirubin, hemoglobinemia, hemoglobinuria), PBS
  (polychromatophlia,Heinz bodies, bite cells
  ),Rate of NADPH generation

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Hemolytic anemia Corpuscular

• 1) Enzyme defect

• G6PD deficiency
• PK deficiency

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Pyruvate kinase deficiency

• Clinical presentation
• a broad spectrum of clinical and hematologic
  findings occurs, ranging from a mild, completely
  compensated hemolytic state to severe anemia.
• Anemia and hyperbilirubinemia may occur in the
  neonatal period.
• In the older patient, pallor, scleral icterus,
  and splenomegaly are usual findings.

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Pyruvate kinase deficiency

•  Laboratory findings
• Elevated reticulocyte count.
• A few small spiculated erythrocytes
• No increased number of spherocytes
• Osmotic fragility is normal.

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Hemolytic anemia Corpuscular

• Enzyme defect
• Membrane defect

• Spherocytosis,
• Elliptocytosis

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Membrane defect Spherocytosis

•  Pathophysiology A deficiency or abnormality of
  the erythrocyte membrane structural protein
  spectrin , ankyrin, band 3, and protein 4.2.
• The spherocyte is relatively rigid and
  non-deformable

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Membrane defect Spherocytosis

• Clinical presentation anemia, hyperbilirubinemia,
  splenomegaly Expansion of the marrow cavities .
• Laboratory findings reticulocytosis, anemia,
  hyperbilirubinemia, spherocyte in PBS, Erythroid
  hyperplasiain BMA, osmotic fragility test,
  Autohemolysis,

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Hemolytic anemia Corpuscular

• 1)Enzyme defect
• 2) Membrane defect
• 3) Hemoglobin disorder

• Normal variant,
• Functional disorder,
• Structural problem,
• Thalassemia

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Hemolytic anemia Hemoglobin disorder

• Normal variant,
• Functional disorder,
• Structural problem,
• Thalassemia

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Hemolytic anemia Extracorpuscular

• Immune
• Nonimmune

• Alloimmune,
• isoimmune,
• Autoimmune

• HUS syndrome,
• TTP,
• DIC,
• Infection,
• Burn,
• Hypersplenism, ..

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Typical Hemolytic Uremic Syndrome

• In the majority of cases, Stx HUS is associated
  with strains of Escherichia coli that produce a
  Shiga toxin
• D HUS associated with Shigella dysenteriae
  serotype 1 will be included in the discussion of
  Stx HUS
• Cases of HUS in children due to Shiga
  toxin-producing E. coli infections other than
  colitis (e.g. UTI) can occur .

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Anemia

• Blood loss (acute)
• Hemolytic anemia
• Impaired red cell formation Normal spleen, low
  retic count, normal bilirubin, normal urinalysis

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Approch to anemia Impaired red cell formation
(Normal spleen, low retic count, normal
bilirubin, normal urinalysis)

• 1)Deficiency
• 2)Bone marrow failure
• 3)Bone marrow infiltration

Iron deficiency Megaloblastic anemia vitamins,
Thyroxine deficiency
Failure of a single cell line Failure of all
cell line
Malignant Non malignant
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Approch to anemia Impaired red cell formation
(Normal spleen, low retic count, normal
bilirubin, normal urinalysis)

• 1)Deficiency
• 2)Bone marrow failure
• 3)Bone marrow infiltration

Iron deficiency Megaloblastic anemia
vitamins Thyroxine deficiency

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Clinical manifestation of IDAHematological
symptoms

• The most common presentation of IDA is an
  otherwise asymptomatic, well nourished infant or
  child who has a mild to moderate microcytic,
  hypochromic anemia

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Clinical manifestation of IDA Non hematological
symptoms

• Neurodevelopmental and Cognitive function
• Immunity
• Exercise capacity
• Pica and pagophagia
• Thrombosis
• Epithelial change dysphagia, esophageal web,
  atrophic glossitis, spoon nails, blue sclerae

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Approch to anemia Impaired red cell formation
(Normal spleen, low retic count, normal
bilirubin, normal urinalysis)

• 1)Deficiency
• 2)Bone marrow failure
• 3)Bone marrow infiltration

Failure of a single cell line CPRA, TEC,
A.crisis Failure of all cell line Aplastic anemia
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Fanconi AnemiaClinical features

• Incidence is 3/1,000,000
• Heterozygote frequency 1/300 in U.S. and Europe
• Median age at diagnosis is 5-7
• Median survival is 20-30 yrs.
• Phenotypic variability occurs even within families

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Frequency of abnormalities in FA
Abnormality Frequency ()

Skeletal (radial ray, hip, vertebral scoliosis, rib) 71
Skin pigmentation (café au lait, hyper- and hypopigmentation) 64
Short stature (median height 5th ile) 63
Eyes (microphthalmia) 38
Renal and urinary tract 34
Male genitalia 20
Mental retardation 16
Gastrointestinal (eg, anorectal, duodenal atresia) 14
Cardiac abnormalities 13
Hearing 11
Central nervous system (eg, hydrocephalus, septum pellucidum) 8
No abnormalities 30


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Approch to anemia Impaired red cell formation
(Normal spleen, low retic count, normal
bilirubin, normal urinalysis)

• 1)Deficiency
• 2)Bone marrow failure
• 3)Bone marrow infiltration

Malignant Leukemia Non malignant Metabolic
disease Osteopetrosis
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Fast Cases
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• A 15 yo girl with a history of systemic lupus
  erythematosus comes to the clinic for evaluation
  of fatigue and pallor.
• Hgb is 7.2, MCV 85, Retic 10, WBC 3.5 (50
  polys, 40 lymphs, 10 atypicals), and plts of
  125.
• The smear shows microspherocytes and rouleaux
  formation. She does not have a history of blood
  loss.
• What does she have?
• Autoimmune hemolytic anemia

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• 17 mounts age infant with an unexplained
  persistent anemia
• History of neonatal jaundice
• Requirement of pRBC transfusion 2 early infancy
• Hb stable 7-9 gr/dl from age 3-17 months
• spleen 5 cm below costal margin
• Retic 20, with indirect hyperbilirubinemia
• What does she have?
• Pyruvate kinase deficiency

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• A 3 yo girl has had diarrhea, sometimes bloody,
  for several days. Now, she has fever, edema,
  petechiae hypertension.
• The CBC shows Hgb 7.5, MCV 79, Retic 15, Plts
  35, and WBC 13.5 with a normal differential. The
  smear shows several helmet cells and
  polychromasia and confirms the thrombocytopenia
• What does she have?
• Hemolytic uremic syndrome

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• A 3 month old boy is brought to the ED lethargic
  and with a fever of 40 C. While attending to
  the airway, correcting hypotension and initiating
  antibiotics, the nurse informs you of the CBC
  results Hgb 5.8, MCV 81, Retic 16, WBC 23.5
  (56 polys, 24 bands, 10 lymphs, 10 atypical
  lymphs) and plts of 350.
• He has blood on dipstick analysis of his urine
  with no RBCs on microscopic analysis.
• The blood shows polychromasia, and several bite
  cells.
• What does he have?
• G6PD deficiency

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• A 9 month old boy comes the Dr.s office for
  evaluation of a cold. Further hx reveals
  introduction of whole cows milk at 5 months and
  no well baby visits.
• He appears quite pale and has the following
  findings Hgb 5.3, MCV 48, plts 780, WBC 12.5
  and retic 1.7
• What does he have?
• Iron Deficiency anemia

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• An 18 month old girl was in good health until she
  developed a cold 10 days ago.
• Now she is pale but without visible jaundice.
• The CBC shows a Hgb of 6.8, MCV of 78 and retic
  of 0.1, WBC Plts are normal as is the
  peripheral blood smear.
• What does she have?
• Transient Erythroblastopenia of
  Childhood

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• The CBC of an 8 yo girl reveals the following
  Hgb 10, MCV 102, Retic 0.4, WBC normal, Plts
  125.
• She is slightly short, has several large
  café-au-lait spots, is performing below average
  in school and has short thumbs.
• What does she have?
• Fanconis Anemia

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• You are asked to assist in the care of political
  refugees from Afghan. On the screening entrance
  exam you note that one of them, a 2 yo girl, is
  very pale and lethargic. Her spleen is down to
  the level of the umbilicus.
• The labs reveal Hgb 6.3, Retic 6, MCV 55, with
  normal WBC plts.
• The smear shows many target cells, polychromasia,
  basophilic stippling, red cell fragment,
  anisocytosis and hypochromia.
• What does she have?
• ? thalassemia major

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People may doubt what you say
but they will believe what you do